Prevalence and Determinants of Opportunistic Infections in HIV Patients: A Cross-Sectional Study in the City of Semarang

Background Opportunistic infection (OI) is the most significant complication of the human immunodeficiency virus (HIV). Differences in the characteristics of HIV patients make the prevalence of Opportunistic infection different between regions. The study aimed to identify variables associated with OI incidence among HIV-infected patients in Semarang City, Indonesia. Methods This study uses secondary data sourced from special HIV surveillance for 2019–2021 with a cross-sectional method. 1362 HIV patients with variables health care facilities; year of diagnosis; area of residence; age; sex; pregnancy status; occupation; risk factors; risk group determined based on purposive sampling were included in the chi-square analysis and logistic regression. Results This study showed 12.3% (n=167) of HIV patients experienced OI, where OI was more common in HIV patients with risk groups of sex workers (28.70%), high-risk partners (18.60%), and Male Sex with Men (MSM) (15.40). The most common types of OI were tuberculosis infection (43%), candidiasis (21%), and diarrhea (9%). Age was the variable most associated with the incidence of OI (p-value 0.001). Conclusions Age groups 45–54 years and 55–64 years have the most influential association with Opportunistic infection incidence in HIV patients, so planning an appropriate intervention program for this subpopulation is necessary.


INTRODUCTION
HIV and AIDS have become a global emergency, one of the most life-threatening infectious diseases, and a severe problem. Without treatment, HIV will gradually destroy the immune system and AIDS (1,2). Globally, 35 million people live with HIV, and 19 million people do not know their HIV-positive status. In Asia, except for Thailand and northern India, most of the HIV infection rate in the general population is less than 1%. In 2012, an estimated 350,000 people in the Asia-Pacific region were newly infected with HIV, of which about 64% were men (3).
Opportunistic Infections (IO) occur due to immune suppression and are believed to be responsible for the development of HIV-related morbidity and mortality (3,4). The most common OI's in HIVinfected patients in Vietnam are oral candidiasis, tuberculosis, wasting syndrome, lower respiratory tract infections, cryptococcosis, and penicilliosis (5). OI are classified according to their severity as WHO clinical stages I to IV. More severe infections are thought to be associated with a poor disease prognosis, and their severity depends on the conditions of exposure to the pathogen, the virulence of the pathogen, and the status of the immune system (6).
The HIV and AIDS epidemic is also a problem in Indonesia, the country with the fifth-highest risk of HIV and AIDS in Asia. Since the first report, new HIV cases have been reported every year. From the first findings in 1987 to December 2018. HIV/AIDS was reported by 460 people (89.5%) in 514 districts and cities in all provinces in Indonesia. As of December 2018, the cumulative number of reported HIV infections was 327,282 (51.1% of the estimated 640,443 in 2016). The cumulative number of people infected with HIV from 1987 to December 2018 was 1.14065 (7,8).
Research conducted in East Java showed that the majority of the AIDS patients in East Java in this sample were male (70.74%), belonged to the adults (26-45 years old) group (62.65%), and worked as employees/laborers (46.08%). In terms of sexual orientation, the majority were heterosexuals (81.81%) or homosexuals (10.63%). The majority of patients experienced one type of opportunistic infection (46.08%), with histoplasmosis (48.77%) and tuberculosis (TB) (42.62%) as the most frequently experienced opportunistic infections (9). Another study in Surabaya showed that heterosexual transmission is a common risk factor in patients. The most prevalent opportunistic infections found in patients were oral candidiasis (58.6%), followed by pulmonary tuberculosis (41.4%) and pneumonia/PCP (41.4%). Other infections found were toxoplasmosis, chronic diarrhea, cytomegalovirus, TB meningitis, hepatitis C, amoebiasis, and cerebritis. Opportunistic infections occurred more often in age ≥40 years and increased as clinical stadiums got worse (10). Based on the description above, this study was conducted to identify variables associated with OI incidence among HIV-infected patients in Semarang, Indonesia.

Data source and subjects:
This study uses secondary data from the HIV surveillance of the Semarang City Health Office. This is a Semarang city-scale survey with a cross-sectional and noninterventional design. The population includes HIV patients who are recorded on the Sistem Informasi HIV-AIDS dan IMS (SIHA) electronic record in 2019 -2020. The data collection was carried out by using interviews, measurements, and examinations. Dependent variable: opportunistic infections declared by health workers Independent variables: Health care facilities were health facilities that report HIV cases categorized by a hospital, public health center (puskesmas), community health center (balkesmas), and Civil Society Organizations (CSO). Year of diagnosis was the year when the respondent was diagnosed with HIV, which was categorized by the years 2019, 2020, and 2021. The region was the residence of respondents who were grouped based on the Semarang area and Outside Semarang. Age was categorized as <15 years, 15-34 years, 35-44 years, 45-54 years, 55-64 years, and >64 years, pregnant status for women who are categorized as yes and no, and employment was grouped based on laborer/driver/housekeeper, fisherman/farmer, private employees, government employees, students, entrepreneurs, and not working/ housewife /retired. Risk factors are grouped into bisex, hetero, homo, drugs, perinatal, etc. Risk groups are grouped into men sex with men, male sex worker, female sex workers, injecting drug users, shemale, sex worker customers, risky couples, etc. Statistical analysis: The data is presented in frequency and percentage based on a traffic accident history. Chi-square analysis was performed to determine the relationship between the independent and dependent variables. P-value <0.05 was considered statistically significant. The independent variable, which has a p-value lower than 0.25, is included in the multivariable analysis. We analyzed the final model using Binary Regression Logistics. All analyzes were performed by SPSS 22.0 (IBM Corporation, NY, USA).

Ethical review: The Health Research Ethics
Committee of Universitas Negeri Semarang has reviewed and approved the protocol by issuing a letter numbered 038/KEPK/EC/2020. No further ethical clearance is required for the analysis of secondary data.

RESULTS
Research findings show that the majority of respondents use hospitals as health care facilities for treatment (59.8%), diagnosed with HIV in 2019 (32.2%), domiciled in Semarang (56.4%), aged 15-34 years (54.3%), male (71.6%), not The details distribution of opportunity infections shows in Figure 1.

Figure 1: Percentage of Opportunistic Infections in HIV patients
The results of statistical tests at table 2 showed several variables that were significantly related to opportunistic infections, including health service facilities (p-value 0.001), year of diagnosis of HIV (pvalue 0.009), age (p-value 0.001), pregnancy status (p-value 0008 ), occupation (p-value 0.002), HIV risk factors (p-value 0.001), and risk group (p-value 0.001). Table 3 show the logistic regression modeling result that show there were 4 models with the last model showing that controlling for other variables, the variables associated with opportunistic infections were year diagnosed (p-value 0.001; AOR 0.678; 95% CI 0.25-0.507), age (p-value 0.001; AOR 1339; 95% CI 1.133-1.582), and risk factors (p-value 0.003; AOR 0.708; 95% CI 0.565-0.886). Age became the most influential variable on opportunistic infection after controlling for other variables.   (12). The research findings show that age is the most influential variable on opportunistic infections after controlling for other variables, the age group 45-54 years and 55-64 years being the most at-risk group; this is following research reports in the United States that people with HIV by age group are generally Globally in 2020 increased in people aged 13-24 years, 35-44 years, and 45-54 years. The diagnosis remains stable among people aged 25-35 years and 55 years and over (13,14). This group has risky behavior.
This study found that work is associated with opportunistic infections. A person who does not work or a housewife who has HIV has a significant relationship to the incidence of opportunistic infections. This is following a study in Ethiopia that found that traders and homemakers are one of the risk factors for the incidence of HIV/AIDS (15,16). Another study regarding the incidence of opportunistic infections in People Living With HIV AIDS at Dr. Kariadi Hospital Semarang obtained different results from this study. The study states that work is not a direct cause of opportunistic infections in People Living With HIV AIDS at Kariadi Hospital, Semarang (17).
The other finding in this study shows that another variable that has a relationship with opportunistic infections is heterosexual risk factors. This research is supported by other research conducted in Indonesia. Research conducted in Gresik and Surabaya found that heterosexuality is a significant risk factor for opportunistic infections in HIV patients. (18,19). Research in Vietnam found that the prevalence of opportunistic infections in HIV patients with heterosexuals reached 81.7% (12). Opportunistic infections that can occur in heterosexual patients infected with HIV are fungal infections Cryptococcus neoformans (20).
This study found an association between the MSM group and the clientele of sex workers with increased OI in HIV patients. Unprotected sexual activity through commercial sex is thought to be linked to Sexual Transmitted Infections. The proportion of using condoms was relatively high in the heterosexual group. The prevalence of Sexual Transmitted Infections was low in this subpopulation, suggesting that other infections may be spread through commercial sex engagement. Certain diseases, including HBV, HCV, HPV, and herpes simplex virus, have been shown to be infected through unprotected sex with an infected partner (21). In addition, the prevalence of certain opportunistic infections associated with sexual transmission among sex workers is significantly high (22,23), indicating a high probability of transmission for heterosexual patients using the service. In seeking other studies that investigated this association and demonstrated only the heterosexual group with an abnormal increase in obtaining IO when buying sex, the results may have important implications for optimizing treatment programs for the two subpopulations (12).
This study has several limitations. First, this is a single-center study; the results may not generalize to the different characteristics of people living with HIV, either internationally or in other parts of Indonesia. Second, analysis with secondary data has been carried out at several different times so that there is limited information for consideration in the discussion and that it does not include factors in the therapy program that must be considered as risk factors (ARV use, adherence, etc.) this is due to the unavailability of these data in the SIHA system. The conclusion of this study is that the 45-54 and 55-64 age groups have the most influential relationship with the incidence of OI in HIV patients; therefore, it is necessary to design an appropriate intervention program for this particular subgroup.